@article{mbs:/content/journal/jgv/10.1099/0022-1317-68-3-913, author = "Nishiyama, Y. and Fujioka, H. and Tsurumi, T. and Yamamoto, N. and Maeno, K. and Yoshida, S. and Shimokata, K.", title = "Effects of the Epipodophyllotoxin VP-16-213 on Herpes Simplex Virus Type 2 Replication", journal= "Journal of General Virology", year = "1987", volume = "68", number = "3", pages = "913-918", doi = "https://doi.org/10.1099/0022-1317-68-3-913", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-68-3-913", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", keywords = "topoisomerase II", keywords = "epipodophyllotoxin", keywords = "HSV-2", abstract = "Summary It has been recently shown that VP-16–213, a semi-synthetic derivative of podophyllotoxin, inhibits the function of mammalian DNA topoisomerase II. In the present study, we examined the effects of VP-16–213 on the replication of herpes simplex virus type 2 (HSV-2). The compound did not inhibit the synthesis of early viral polypeptides at concentrations at which viral DNA synthesis was strongly suppressed, but induced double-strand breaks in newly synthesized HSV DNA. Electron microscopic examination of treated cells revealed the presence of a number of capsids with empty or partial cores. The level of topoisomerase II activity remained unaltered after infection, and all attempts to isolate VP-16–213-resistant mutants of HSV-2 have failed in spite of extensive efforts. It is suggested therefore that the mode of action of VP-16–213 may be inhibition of viral DNA synthesis by impairing the function of host cell topoisomerase II.", }